It is commonly known that increased muscle mass, strength and extended muscular performance occur in the most effective manner when exercise routines are done to complete exhaustion. However, during extended periods of exercise, metabolites from the breakdown of adenosine triphosphate (ATP), mainly hydrogen ions (H+), begin to accumulate leading to a decline in the pH levels of blood and muscle, which can be problematic or undesirable. The increase in acidity of the muscle, as a result of the accumulation of H+ ions, is directly linked to muscle fatigue, which ultimately causes a decrease in the duration of intensive bouts of exercise (Cooke R, Pate E. The effects of ADP and phosphate on the contraction of muscle fibers. Biophys J. 1985 November; 48(5):789-98). This fatigue is a result of inhibition of enzymes, by decreased pH, which are vital for energy production and the force-producing capacity of muscles (Febbraio M A, Dancey J. Skeletal muscle energy metabolism during prolonged, fatiguing exercise. J Appl Physiol. 1999 December; 87(6):2341-7).
Carnosine is one of the most effective buffers, or pH stabilizers, in human skeletal muscle, and as such is very efficient at mopping up excess H+ ions. When carnosine is ingested as food, it must be broken down to its constituent amino acids (β-alanine and histidine) in order cross cell membranes, after which it is then reassembled. Due to lack of absorption, in addition to the financial cost of the raw material, carnosine, administration of the constituent amino acids has been explored. For example, administration of exogenous β-alanine has been shown to increase the levels of carnosine in skeletal muscle cells (Bate-Smith E C. The buffering of muscle in rigour: protein, phosphate, and carnosine. J Physiol. 1938; 92:336-43).
Additionally, other methods for increasing the duration of exercise have been explored. One such method is the administering of compounds that are essential for ATP synthesis and are depleted during exhaustive exercise, such as malic acid. Malic acid is a naturally occurring compound found in a large number of fruits and vegetables, as well as all living cells; which plays a key role in the transportation of NADH from the cytosol to the mitochondria for energy production (ATP production). Malic acid is part of the initiation of the Krebs cycle and is one of the only metabolites that actually decrease in concentration during exercise. Thus, administration of exogenous malic acid will result in increased ATP production as a result of attenuation of malic acid depletion.
Supplementation with other deprotonated organic acids can be used for attenuation of metabolic acidosis. For example, citrate lacks all of its acidic protons, yielding three carboxylate functionalities that can readily take up free protons. Since all of acidic protons are removed, the citrate has three sites which are capable of taking up free protons in serum and working muscle. Therefore, administration of deprotonated organic acids can inhibit the decrease in pH, which is a result of ATP hydrolysis, thereby leading to less fatigue resulting from the inhibition of enzymes that are vital for energy production and the force-producing capacity of muscles.